休眠の臨床応用に向けて： マウスを用いた能動的低代謝の研究

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  • Toward clinical application of torpor: active hypometabolism research in mice

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<p>Some mammals enter a hypometabolic state either daily torpor (minutes to hours in length) or hibernation (days to weeks), when reducing metabolism would benefit survival. The metabolic rate drops to 1～30% of normal rates, and animals sacrifice their vital biological functions such as consciousness and mobility to save metabolism, which makes them look offline. The mechanisms for such hypothermia-resistance and hypometabolism-resistance is not understood.</p><p>Hibernators demonstrate deep torpor by reducing both the sensitivity (H) and the theoretical set-point temperature (TR) of the thermogenesis system, resulting in extreme hypothermia close to ambient temperature (TA). We have developed a stable torpor induction method for mice and evaluated minimal body temperature (TB) and oxygen consumption rate (VO2) of fasting-induced torpor in C57BL/6J mice (B6J) under various TAs. As in hibernators, H decreased 91.5% during daily torpor while TR only decreased 3.79 °C in mice (Sunagawa GA and Takahashi M, Sci Rep, 2016). Furthermore, we have found that C57BL/6N (B6N) has a higher metabolic rate during torpor than B6J (GA Sunagawa, 2018, BioRxiv 374975).</p><p>Interestingly, in both B6J and B6N mice strains, H is decreased as hibernators, but TR remains relatively unchanged during daily torpor. To investigate whether the stable TR during torpor is a common feature in mice, we have evaluated various inbred strains and found that in some strains, TR may be reduced than B6J or B6N mice. Because TR is suspected to be controlled centrally in mammals, we are attempting to control TR by stimulating the central nervous system.</p>

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